Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

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??Objective    To observe the effects of lithium chloride pretreatment on cognitive ability of aged rats after oral and maxillofacial surgery. Methods    A total of 48 aged male SD rats??18 ~ 20 months old??weight 550 ~ 700 g?? were bought from the Experimental Animal Center of China Medical University . These rats were randomly divided into three groups??including the normal control group??group C??n=16????surgery and anesthesia group??group O??n=16????and lithium chloride preconditioning group??group L??n=16??.Rats in each group were randomly divided into two parts??one part was given Morris water maze test three days after the surgery and its characteristics of behavior tested. Another part was decapitated 24 h after the surgery and extracted and the hippocampus brain separated at the same time. Test expression content of IL-1β GSK-3β p-GSK-3β??ser9??in the hippocampus by Elisa and Western blotting detection method respectively. Results    Morris water maze test showed that??the first day after surgery??latencies of group L and O were significantly longer than group C??compared with group C in swimming distance?? latency and swim distances of group L were shorter than group O. With the comparison of multiple analysis of variance??differences were statistically significant??P??0.05??. Groups L and O in the second day were slightly shortened compared to the first day??on the third day after surgery it has also improved over the second day. Space exploration experiments in rats showed that??the dwell time of group C was significantly longer in the platform quadrant and the frequency of crossing the platform also increased compared with groups L and O. In addition??group L and group O were higher in IL-β levels than group C??the difference being statistically significant by analysis of variance??P??0.05????but group L was significantly lower compared with group O??the difference being statistically significant??P??0.05??. The content of GSK-3β of three groups were of no significant difference??P > 0.05????but p-GSK-3β??ser9??content was significantly lower in group L and O than in group C. The content of GSK-3β of group L was higher than in group O??the difference being statistically significant??P??0.05??. Conclusion    Pretreatment with lithium chloride in postoperative aged rats can inhibit the expression of inflammatory cytokines and increase GSK-3β phosphorylation in the hippocampus cells??so p-GSK-3β??ser9??upregulates and inhibites  the apoptosis of brain cells??thereby improved cognitive abilities after the cavity and maxillofacial surgery.     

Epidemiological evidence of increased waist circumference,but not body mass index,associated with impaired baroreflex sensitivity

Although an inverse relationship between body mass index (BMI) and baroreflex sensitivity (BRS) was found, the effect of waist circumference (WC) on BRS is still inconclusive. The contradictory results of previous studies may be related to the heterogeneity and relatively small sample size of the subjects examined. The aim of this population-based study was to investigate whether the influence of increased WC is more detrimental to BRS than BMI. A total of 760 community dwellers were recruited and they were classified into Q1 (n = 189), Q2 (n = 183), Q3 (n = 192) and Q4 (n = 196) groups, based on WC quartiles. Spontaneous BRS was determined by spectral α coefficient method. Valsalva ratio was the longest RR interval after release of Valsalva maneuver divided by the shortest RR interval during maneuver. Cardiac autonomic function was calculated by power spectrum of heart rate in low and high frequency (LF, 0.04–0.15 Hz; HF, 0.15–0.40 Hz), and LF/HF ratio in supine position for five minutes. There were significant differences in spontaneous BRS and Valsalva ratio among different WC groups. In multivariate analysis, obesity was inversely associated with spontaneous BRS and Valsalva ratio. However, these inverse relationships became insignificant after further adjustment for WC quartiles. In contrast, Q4 vs. Q1, Q3 vs. Q1 and Q2 vs. Q1 of WC were inversely related to spontaneous BRS. Q4 vs. Q1 and Q3 vs. Q1 of WC were negatively associated with the Valsalva ratio. In conclusion, increased and even high-normal WC had a stronger adverse effect on BRS than BMI, independent of cardio-metabolic risk factors.     

Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

Gaining weight through retirement? Results from the SHARE survey

This paper estimates the causal impact of retirement on the Body Mass Index (BMI) of adults aged 50–69 years old, on the probability of being either overweight or obese and on the probability of being obese. Based on the 2004, 2006 and 2010–2011 waves of the Survey of Health, Ageing and Retirement in Europe (SHARE), our identification strategy exploits variation in European Early Retirement Ages (ERAs) and stepwise increases in ERAs in Austria and Italy between 2004 and 2011 to examine an exogenous shock to retirement behavior. Our results show that retirement induced by discontinuous incentives in early retirement schemes causes a 12-percentage point increase in the probability of being obese among men within a two- to four-year period. We find that the impact of retirement is highly non-linear and mostly affects the right-hand side of the male BMI distribution. Additional results show that this pattern is driven by men retiring from strenuous jobs and by those who were already at risk of obesity. In contrast, no significant results are found among women.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.